55 research outputs found

    Mitochondrial genomes as living ‘fossils’

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    Fragile finance: The revenue models of oppositional news outlets in repressive regimes

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    For journalists promoting the free flow of information in repressive or restrictive media environments, the issue of financial sustainability is complex. Both media in exile (out-of-country news outlets feeding independent information into the country of origin) and news outlets in restrictive news environments (in-country providing counter-information) exist in flawed market situations and often rely on grant funding. This is the first academic study of the revenue streams of these media, providing scarce empirical data and a typology of funding structures of these media. This article examines three main revenue categories: grant funding, earned income and donations. The major factors influencing revenue streams compared to online media startups in open markets are discussed. The article finds significant barriers to revenue creation and identifies the need for alternative approaches, particularly partnerships, to promote economic resilience for media under threat

    Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

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    Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty

    Molecular insights into the premature aging disease progeria

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    LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs

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    Regulation of mtDNA expression is critical for maintaining cellular energy homeostasis and may, in principle, occur at many different levels. The leucine-rich pentatricopeptide repeat containing (LRPPRC) protein regulates mitochondrial mRNA stability and an amino-acid substitution of this protein causes the French-Canadian type of Leigh syndrome (LSFC), a neurodegenerative disorder characterized by complex IV deficiency. We have generated conditional Lrpprc knockout mice and show here that the gene is essential for embryonic development. Tissue-specific disruption of Lrpprc in heart causes mitochondrial cardiomyopathy with drastic reduction in steady-state levels of most mitochondrial mRNAs. LRPPRC forms an RNA-dependent protein complex that is necessary for maintaining a pool of non-translated mRNAs in mammalian mitochondria. Loss of LRPPRC does not only decrease mRNA stability, but also leads to loss of mRNA polyadenylation and the appearance of aberrant mitochondrial translation. The translation pattern without the presence of LRPPRC is misregulated with excessive translation of some transcripts and no translation of others. Our findings point to the existence of an elaborate machinery that regulates mammalian mtDNA expression at the post-transcriptional level
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